P-105 Glycine attenuates impairments of interhemispheric gamma-band connectivity in the ketamine model of schizophrenia

Background: In patients with schizophrenia alterations in auditory perception are common. Disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism causing Excitatory-to-inhibitory (E/I) imbalance, altered connectivity and changes in auditory perception in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist as well as glycine, a glutamate N-Methyl-D-Aspartate receptor (NMDAR)-coagonist on mechanisms underlying interhemispheric gamma-band connectivity and conscious auditory perception during dichotic listening (DL).

Methods: In a double-blind, randomized, placebo-controlled crossover design, 25 n healthy volunteers were measured using 64-channel-electroencephalography (EEG). Psychopathologic changes were assessed by PANSS and the subjective 5D-ASC questionnaire.

Results: Interhemispheric connectivity analysis were performed using eLORETA source estimation and lagged phase synchronization (LPS) in the gamma-band range (30–100 Hz). Ketamine induced a schizophrenia-like change in laterality of dichotic hearing that could be reversed by glycine-modulation. In addition, interhemispheric gamma-band connectivity was found to be altered both under ketamine and glycine (higher interhemispheric gamma-band connectivity). Pretreatment with glycine normalized the ketamine-induced alterations of interhemispheric connectivity.

Conclusion: These findings argue for an important role of glutamatergic neurotransmission for the interhemispheric communication between bilateral auditory cortices. NMDAR-modulation could help to restore E/I-imbalance causing disturbed auditory perception in schizophrenia.